Spontaneous injury in isolated sheep lungs: role of perfusate leukocytes and platelets

1989 ◽  
Vol 66 (3) ◽  
pp. 1287-1296 ◽  
Author(s):  
D. B. Pearse ◽  
R. G. Brower ◽  
N. F. Adkinson ◽  
J. T. Sylvester
Keyword(s):  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Pressure Ratio ◽  
Pulmonary Sequestration ◽  
Dry Weight ◽  
Lymph Flow ◽  
Thromboxane B2 ◽  
Pulmonary Arterial ◽  
Lung Lymph ◽  
Lung Lymph Flow

Perfusion of isolated sheep lungs with blood causes spontaneous edema and hypertension preceded by decreases in perfusate concentrations of leukocytes (WBC) and platelets (PLT). To determine whether these decreases were caused by pulmonary sequestration, we continuously measured blood flow and collected pulmonary arterial and left atrial blood for cell concentration measurements in six lungs early in perfusion. Significant sequestration occurred in the lung, but not in the extracorporeal circuit. To determine the contribution of these cells to spontaneous injury in this model, lungs perfused in situ with a constant flow (100 ml.kg-1.min-1) of homologous leukopenic (WBC = 540 mm-3, n = 8) or thrombocytopenic blood (PLT = 10,000 mm-3, n = 6) were compared with control lungs perfused with untreated homologous blood (WBC = 5,320, PLT = 422,000, n = 8). Perfusion of control lungs caused a rapid fall in WBC and PLT followed by transient increases in pulmonary arterial pressure, lung lymph flow, and perfusate concentrations of 6-ketoprostaglandin F1 alpha and thromboxane B2. The negative value of reservoir weight (delta W) was measured as an index of fluid entry into the lung extravascular space during perfusion. delta W increased rapidly for 60 min and then more gradually to 242 g at 180 min. This was accompanied by a rise in the lymph-to-plasma oncotic pressure ratio (pi L/pi P). Relative to control, leukopenic perfusion decreased the ratio of wet weight to dry weight, the intra- plus extravascular blood weight, and the incidence of bloody lymph. Thrombocytopenic perfusion increased lung lymph flow and the rate of delta W, decreased pi L/pi P and perfusate thromboxane B2, and delayed the peak pulmonary arterial pressure. These results suggest that perfusate leukocytes sequestered in the lung and contributed to hemorrhage but were not necessary for hypertension and edema. Platelets were an important source of thromboxane but protected against edema by an unknown mechanism.

Hypoxia and angiotensin II infusion redistribute lung blood flow in lambs

1985 ◽  
Vol 58 (3) ◽  
pp. 812-818 ◽  
Author(s):  
T. N. Hansen ◽  
A. L. Le Blanc ◽  
A. L. Gest
Keyword(s):  
Blood Flow ◽  
Angiotensin Ii ◽  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Lymph Flow ◽  
Filtration Pressure ◽  
Alveolar Hypoxia ◽  
Pulmonary Arterial ◽  
Lung Lymph ◽  
Lung Lymph Flow

To assess the effects of alveolar hypoxia and angiotensin II infusion on distribution of blood flow to the lung we performed perfusion lung scans on anesthetized mechanically ventilated lambs. Scans were obtained by injecting 1–2 mCi of technetium-labeled albumin macroaggregates as the lambs were ventilated with air, with 10–14% O2 in N2, or with air while receiving angiotensin II intravenously. We found that both alveolar hypoxia and infusion of angiotensin II increased pulmonary vascular resistance and redistributed blood flow from the mid and lower lung regions towards the upper posterior region of the lung. We assessed the effects of angiotensin II infusion on filtration pressure in six lambs by measuring the rate of lung lymph flow and the protein concentration of samples of lung lymph. We found that angiotensin II infusion increased pulmonary arterial pressure 50%, lung lymph flow 90%, and decreased the concentration of protein in lymph relative to plasma. These results are identical to those seen when filtration pressure increases during alveolar hypoxia. We conclude that alveolar hypoxia and angiotensin II infusion both increase fluid filtration in the lung by increasing filtration pressure. The increase in filtration pressure may be the result of a redistribution of blood flow in the lung with relative overperfusion of vessels in some areas and transmission of the elevated pulmonary arterial pressure to fluid-exchanging sites in those vessels.

BW-755C diminishes smoke-induced pulmonary edema

1995 ◽  
Vol 78 (1) ◽  
pp. 64-69 ◽  
Author(s):  
C. A. Hales ◽  
S. Musto ◽  
W. G. Hutchison ◽  
E. Mahoney
Keyword(s):  
Pulmonary Edema ◽  
Pulmonary Arterial Pressure ◽  
Dry Weight ◽  
Lymph Flow ◽  
Smoke Inhalation ◽  
Lipoxygenase Inhibitor ◽  
Common Component ◽  
Flow Change ◽  
Pulmonary Arterial ◽  
Lung Lymph

Pulmonary edema following smoke inhalation is due to the chemical toxins in smoke and not to the heat. We have shown that acrolein, a common component of smoke, induces pulmonary edema, perhaps via release of leukotrienes. We, therefore, hypothesized that acrolein, a component of smoke from burning cotton, might have a major role in producing pulmonary edema in sheep after cotton smoke inhalation and that BW-755C, a combined cyclo- and lipoxygenase inhibitor, would prevent the edema, whereas indomethacin, a cyclooxygenase inhibitor, would not. In control anesthetized sheep (n = 7), 128 breaths of cotton smoke induced no change in pulmonary arterial pressure but induced increases (P < 0.05) in pulmonary lymph flow from 4.4 +/- 0.8 (SE) to 15 +/- 2.7 ml/h, lymph protein flux from 0.25 +/- 0.08 to 0.80 +/- 0.16 g/h, and blood-corrected wet-to-dry weight ratios from a normal value of 3.8 +/– 0.07 (n = 9) to 4.5 +/- 0.18. Indomethacin (n = 6) did not significantly prevent these changes, whereas BW-755C decreased lung lymph flow change from 5 +/- 1 to 7 +/- 2 ml/h (P = NS), lymph protein flux from 0.25 +/- 0.08 to 0.35 +/- 0.1 g/h (P = NS), and weight-to-dry ratio from normal to 3.9 +/- 2.1 (P = NS). These data suggest leukotrienes may have a role in producing cotton smoke-induced noncardiogenic pulmonary edema.

Cyclooxygenase and lipoxygenase inhibition by BW-755C reduces acrolein smoke-induced acute lung injury

1994 ◽  
Vol 77 (2) ◽  
pp. 888-895 ◽  
Author(s):  
S. P. Janssens ◽  
S. W. Musto ◽  
W. G. Hutchison ◽  
C. Spence ◽  
M. Witten ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Arterial Pressure ◽  
Pulmonary Edema ◽  
Pulmonary Arterial Pressure ◽  
Weight Ratio ◽  
Peak Inspiratory Pressure ◽  
Dry Weight ◽  
Lymph Flow ◽  
Pulmonary Arterial ◽  
Arterial Po2

Inhalation of smoke containing acrolein, the most common toxin in urban fires after carbon monoxide, causes vascular injury with non-cardiogenic pulmonary edema containing potentially edematogenic eicosanoids such as thromboxane (Tx) B2, leukotriene (LT) B4, and the sulfidopeptide LTs (LTC4, LTD4, and LTE4). To determine which eicosanoids are important in the acute lung injury, we pretreated sheep with BW-755C (a combined cyclooxygenase and lipoxygenase inhibitor), U-63557A (a specific Tx synthetase inhibitor), or indomethacin (a cyclooxygenase inhibitor) before a 10-min exposure to a synthetic smoke containing carbon particles (4 microns) with acrolein and compared the results with those from control sheep that received only carbon smoke. Acrolein smoke induced a fall in arterial PO2 and rises in peak inspiratory pressure, main pulmonary arterial pressure, pulmonary vascular resistance, lung lymph flow, and the blood-free wet-to-dry weight ratio. BW-755C delayed the rise in peak inspiratory pressure and prevented the fall in arterial PO2, the rise in lymph flow, and the rise in wet-to-dry weight ratio. Neither indomethacin nor U-63557A prevented the increase in lymph flow or wet-to-dry weight ratio, although they did blunt and delay the rise in airway pressure and did prevent the rises in pulmonary arterial pressure and pulmonary vascular resistance. Thus, cyclooxygenase products, probably Tx, are responsible for the pulmonary hypertension after acrolein smoke and to some extent for the increased airway resistance but not the pulmonary edema. Prevention of high-permeability pulmonary edema after smoke with BW-755C suggests that LTB4, may be etiologic, as previous work has eliminated LTC4, LTD4, and LTE4.

Cyclooxygenase inhibition during phorbol-induced granulocyte stimulation in awake sheep

1984 ◽  
Vol 56 (4) ◽  
pp. 999-1007 ◽  
Author(s):  
J. H. Newman ◽  
J. E. Loyd ◽  
M. L. Ogletree ◽  
B. O. Meyrick ◽  
K. L. Brigham
Keyword(s):  
Pulmonary Hypertension ◽  
Arachidonic Acid ◽  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Thromboxane B2 ◽  
Base Line ◽  
Plasma Protein Concentration ◽  
Pulmonary Vascular Permeability ◽  
Pulmonary Arterial ◽  
Lung Lymph

In vitro, phorbol myristate acetate (PMA) causes sheep granulocytes to release superoxide. Infused into sheep, PMA causes leukopenia, hypoxemia, pulmonary hypertension, and increased flow of protein-rich lung lymph. Lung lymph thromboxane B2 and 6-ketoprostaglandin F1 alpha levels rise markedly after PMA infusion. To see whether cyclooxygenase products of arachidonic acid mediate the lung vascular responses to PMA, we infused 5 micrograms/kg PMA twice in each of six sheep, once in the presence of sodium meclofenamate and once alone. We varied the order of paired experiments and allowed 4–7 days between experiments. Meclofenamate (5 mg/kg loading dose + 3 mg X kg-1 X h-1 infusion) given alone had no effect on base-line variables. Meclofenamate inhibited or delayed the initial pulmonary hypertension and hypoxemia after PMA but exaggerated the later increase in pulmonary arterial pressure; it prevented any increase in thromboxane B2 and 6-ketoprostaglandin F1 alpha after PMA. Meclofenamate did not affect the degree of leukopenia or the severity of the later hypoxemia nor did it prevent accumulation of granulocytes in the lung. Lung lymph flow was higher with meclofenamate + PMA than with PMA alone, but lymph-to-plasma protein concentration ratio was lower, suggesting that the main effect of meclofenamate on lymph production after PMA was related to the degree of pulmonary hypertension. We conclude that the early increase in pulmonary arterial pressure caused by PMA is mediated by a cyclooxygenase product of arachidonic acid, possibly thromboxane A2, but the later pulmonary hypertension and the increase in pulmonary vascular permeability are not the result of cyclooxygenase products.

Intravascular macrophage depletion attenuates endotoxin lung injury in anesthetized sheep

1999 ◽  
Vol 87 (4) ◽  
pp. 1354-1359 ◽  
Author(s):  
Yasuyuki Sone ◽  
Vladimir B. Serikov ◽  
Norman C. Staub
Keyword(s):  
Protein Concentration ◽  
Pulmonary Arterial Pressure ◽  
Lymph Flow ◽  
Plasma Protein Concentration ◽  
Macrophage Population ◽  
Protein Clearance ◽  
Pulmonary Arterial ◽  
Lung Lymph ◽  
Pulmonary Intravascular Macrophages ◽  
Lung Lymph Flow

We recently showed that we can selectively and safely deplete most (average 85%) of the pulmonary intravascular macrophages in sheep by intravenously infusing liposomes containing dichloromethylene bisphosphonate. After a 1-h stable baseline, we made a 6-h comparison after a 30-min intravenous endotoxin infusion (1 μg/kg) between six anesthetized control lambs and six anesthetized lambs in which the intravascular macrophages had been depleted 24 h previously. Three of the control lambs had been macrophage depleted and allowed to recover their intravascular macrophage population for ≥2 wk. After depletion, both the early and late pulmonary arterial pressure rises were dramatically attenuated. Our main interest, however, was in the acute lung microvascular injury response. The early and late rises in lung lymph flow and the increase in lung lymph protein clearance (lymph flow × lymph-to-plasma protein concentration ratio) were >90% attenuated. We conclude the pulmonary intravascular macrophages are responsible for most of the endotoxin-induced pulmonary hypertension and increased lung microvascular leakiness in sheep, although the unavoidable injury of other intravascular macrophages by the depletion regime may also contribute something.

Chronic lung lymph fistula that only drains the left lung

1995 ◽  
Vol 269 (4) ◽  
pp. R943-R947
Author(s):  
Y. Kikuchi ◽  
H. Nakazawa ◽  
D. L. Traber
Keyword(s):  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Mediastinal Lymph Node ◽  
Pulmonary Veins ◽  
Pulmonary Arteries ◽  
Left Lung ◽  
Lymph Flow ◽  
Pulmonary Arterial ◽  
The Right ◽  
Arteries And Veins

We developed a chronic lung fistula that drains only the left lung, allowing for evaluation of injury in a single lung. To remove lymph drainage from the right lung into the caudal mediastinal lymph node, the right lower pulmonary ligament was severed. Pneumatic occluders were placed on the left pulmonary arteries and veins. To ensure that lymph drained from only the left lung, we increased the right pulmonary arterial pressure (RPAP) from 21.2 +/- 0.5 to 36.5 +/- 0.6 mmHg. The left pulmonary arterial pressure (LPAP) was kept at wedge pressure level for 1 h by inflating pneumatic occluders. Lymph flow from the left lung fistula was stable during this occlusion. Six hours after recovery was increased the LPAP from a baseline level of 19.1 +/- 1.0 to 36.4 +/- 0.9 mmHg and the RPAP from 21.2 +/- 0.5 to 38.0 +/- 0.8 mmHg for 2 h by inflating the pneumatic occluders on the left and right pulmonary veins. Lymph flow increased from 5.3 +/- 1.0 to 28.0 +/- 2.9 ml/h. Reflection coefficient was calculated at 0.80 +/- 0.02.

Effect of interstitial edema on lung lymph flow in goats in the absence of filtration

1992 ◽  
Vol 72 (3) ◽  
pp. 1142-1148 ◽  
Author(s):  
K. Kambara ◽  
K. E. Longworth ◽  
V. B. Serikov ◽  
N. C. Staub
Keyword(s):  
Lymph Flow ◽  
Alveolar Wall ◽  
Half Time ◽  
Interstitial Edema ◽  
Lung Water ◽  
Pulmonary Arterial ◽  
The Mean ◽  
Lung Lymph ◽  
Normal Lungs ◽  
Lung Lymph Flow

We tested the effect of interstitial edema on lung lymph flow when no filtration occurred. In 16 anesthetized open-thorax ventilated supine goats, we set pulmonary arterial and left atrial pressures to nearly zero and measured lymph flow for 3 h from six lungs without edema and ten with edema. Lymph flow decreased exponentially in all experiments as soon as filtration ceased. In the normal lungs the mean half time of the lymph flow decrease was 12.7 +/- 4.8 (SD) min, which was significantly shorter (P less than 0.05) than the 29.1 +/- 14.8 min half time in the edematous lungs. When ventilation was stopped, lymph flow in the edematous lungs decreased as rapidly as in the normal lungs. The total quantity of lymph after filtration ceased was 2.7 +/- 0.8 ml in normal lungs and 9.5 +/- 6.3 ml in edematous lungs, even though extravascular lung water was doubled in the latter (8.4 +/- 2.4 vs. 3.3 +/- 0.4 g/g dry lung, P less than 0.01). Thus the maximum possible clearance of the interstitial edema liquid by the lymphatics was 6.3 +/- 4.8%. When we restarted pulmonary blood flow after 1–2 h in four additional goats, lymph flow recovered within 30 min to the baseline level. These findings support the hypothesis that lung lymph flow originates mainly from alveolar wall perimicrovascular interstitial liquid and that the contribution of the lung lymphatic system to the clearance of interstitial edema (bronchovascular cuffs, interlobular septa) is small.

Permeability of barriers to albumin flux in lungs of sheep resuscitated from hemorrhagic shock

1986 ◽  
Vol 61 (6) ◽  
pp. 2156-2161 ◽  
Author(s):  
A. B. Gorin ◽  
G. Mendiondo
Keyword(s):  
Hemorrhagic Shock ◽  
Extravascular Lung Water ◽  
Weight Ratio ◽  
Equilibrium Concentration ◽  
Dry Weight ◽  
Lymph Flow ◽  
Base Line ◽  
Lung Water ◽  
Lung Lymph ◽  
Lung Lymph Flow

We assessed pulmonary endothelial and epithelial permeability and lung lymph flow in nine adult sheep under base-line conditions and after resuscitation from profound hemorrhagic shock. Animals were mechanically ventilated and maintained on 1% halothane anesthesia while aortic pressure was held at 40 Torr for 3 h. Systemic heparin was not used. After reinfusion of shed blood, sheep recovered from anesthesia and we measured lung lymph flow (QL), lymph-to-plasma concentration ratio for proteins, and time taken to reach half-equilibrium concentration of intravenous tracer albumin in lymph (t1/2). Twenty-four hours after bolus injection of radio-albumin we lavaged subsegments of the right upper lobe and determined fractional equilibration of the tracer in the alveolar luminal-lining layer. In each sheep we had measured these parameters 7 days earlier under base-line conditions. Animals were killed, and the lungs were used for gravimetric determination of extravascular lung water (gravimetric extravascular lung water-to-dry weight ratio) 24 h after resuscitation from shock. Pulmonary endothelial injury after resuscitation was evidenced by marked increase in QL, without fall in lymph-to-plasma ratio. Time taken to reach half-equilibrium concentration fell from 169 +/- 47 (SD) min in base-line studies to 53 +/- 33 min after shock. There was no evidence of lung epithelial injury. Gravimetric extravascular lung water-to-dry weight ratio was significantly increased in these animals killed 24 h after resuscitation (4.94 +/- 0.29) compared with values in our laboratory controls (4.13 +/- 0.09, mean +/- SD). These data demonstrate a loss of lung endothelial integrity in sheep after resuscitation from profound hemorrhagic shock.

Inspiratory airway obstruction does not affect lung fluid balance in lambs

1985 ◽  
Vol 58 (4) ◽  
pp. 1314-1318 ◽  
Author(s):  
T. N. Hansen ◽  
A. L. Gest ◽  
S. Landers
Keyword(s):  
Airway Obstruction ◽  
Endotracheal Tube ◽  
Fluid Balance ◽  
Left Atrial ◽  
Lymph Flow ◽  
Lung Fluid ◽  
Lung Fluid Balance ◽  
Pulmonary Arterial ◽  
Lung Lymph ◽  
Lung Lymph Flow

The purpose of this study was to examine the effects of inspiratory airway obstruction on lung fluid balance in newborn lambs. We studied seven 2- to 4-wk-old lambs that were sedated with chloral hydrate and allowed to breathe 30–40% O2 spontaneously through an endotracheal tube. We measured lung lymph flow, lymph and plasma protein concentrations, pulmonary arterial and left atrial pressures, mean and phasic pleural pressures and airway pressures, and cardiac output during a 2-h base-line period and then during a 2- to 3-h period of inspiratory airway obstruction produced by partially occluding the inspiratory limb of a nonrebreathing valve attached to the endotracheal tube. During inspiratory airway obstruction, both pleural and airway pressures decreased 5 Torr, whereas pulmonary arterial and left atrial pressures each decreased 4 Torr. As a result, calculated filtration pressure remained unchanged. Inspiratory airway obstruction had no effect on steady-state lung lymph flow or the lymph protein concentration relative to that of plasma. We conclude that in the spontaneously breathing lamb, any decrease in interstitial pressure resulting from inspiratory airway obstruction is offset by a decrease in microvascular hydrostatic pressure so that net fluid filtration remains unchanged.

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